Skin cancer incidence continues to increase. Over 500,000 basal (BCC) and cutaneous squamous cell (SCC) cancers are newly diagnosed in the United States each year with a disproportionate incidence in Arizona and throughout the southern U.S. The long-term goal of this proposal is to reduce the incidence, morbidity and costs from skin cancer. Results from this proposal will also influence cancer prevention research for other cancer types. To accomplish this goal, a randomized, double-blinded skin cancer prevention trial will be conducted in subjects with a history of multiple actinic keratoses. The specific aims of the trial include: 1)To motivate and determine the frequency and degree of protocol adherence of the 2298 subjects randomized to retinol or placebo. 2)To determine the frequency, type and degree of adverse or protective health effects. 3)To compare the incidence rate and the time to diagnosis of BCC, SCC and BCC+SCC, separately, by medication group. 4)To determine plasma concentrations of retinol and a vitamin A fatty acid ester (retinyl palmitate) for each subjects' initial visit and for selected subjects at their follow-up visits. 5)After completion of the medication phase of the trial (1993), to determine if the incidence of newly diagnosed BCC or SCC rebounds (increases) after stopping medication. 6)To accurately and precisely analyze the levels of retinol, retinyl palmitate and retinoic acid in cutaneous tissue and buccal mucosal cells in a sample of supplemented and non supplemented study subjects. 7)To evaluate the association of each retinoid in cutaneous tissue, buccal mucosal cells and plasma adjusting for medication group and subjects characteristics including age, dietary status, smoking status, and other factors.